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 Dacarbazine

Dacarbazine  is a triazene derivative with antineoplastic activity. Dacarbazine alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Dacarbazine gained FDA approval in May 1975 as DTIC-Dome. The drug was initially marketed by Bayer. DTlC-Dome Sterile (dacarbazine) is a colorless to an ivory colored solid which is light sensitive. Each vial contains 100 mg of dacarbazine, or 200 mg of dacarbazine (the active ingredient), anhydrous citric acid and mannitol. DTlC-Dome is reconstituted and administered intravenously (pH 3–4). DTlC-Dome is an anticancer agent. DTlC-Dome is indicated in the treatment of metastatic malignant melanoma. In addition, DTlC-Dome is also indicated for Hodgkin's disease as a second-line therapy when used in combination with other effective agents.

CLINICAL PHARMACOLOGY:

After intravenous administration of DTlC-Dome, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours.1 In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours.1 The average cumulative excretion of unchanged DTlC in the urine is 40% of the injected dose in 6 hours.1 DTlC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations DTIC is not appreciably bound to human plasma protein. In man, DTlC is extensively degraded. Besides unchanged DTlC, 5-aminoimidazole -4 carboxamide (AlC) is a major metabolite of DTlC excreted in the urine. AlC is not derived endogenously but from the injected DTlC, because the administration of radioactive DTlC labeled with 14C in the imidazole portion of the molecule (DTlC-2-14C) gives rise to AIC-2-14C1. Although the exact mechanism of action of DTIC-Dome is not known, three hypotheses have been offered:
1. inhibition of DNA synthesis by acting as a purine analog
2. action as an alkylating agent
3. interaction with SH groups. 

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